Abstract P342: Periodontal Bacteria, Prevalent Prediabetes and Plasma Glucose Progression: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS)

Introduction: Periodontal infections have been hypothesized as a cardiometabolic risk factor. The relationship between periodontal microbiota and early diabetes risk has not been studied. Hypothesis: We hypothesized that periodontopathic bacteria would be associated with both prevalent pre diabetes and accelerated longitudinal plasma glucose progression among diabetes-free adults. Methods: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 300 diabetes-free adults (77% female) aged 20-55 years (mean=34±10). Prevalent prediabetes was defined as: i) 5.6%<HbA1C<6.5%; or ii) 99 mg/dL<fasting plasma glucose (FPG)<126 mg/dL. In 1,188 subgingival plaque samples, 11 bacterial species including Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Treponema denticola (Td), Tannerella forsythia (Tf) and Actinomyces naeslundii (An) were assessed at baseline. Modified Poisson regression evaluated prediabetes prevalence across bacterial tertiles. Risk ratios (RR), 95% confidence intervals (CI) for 3rd vs. 1st tertile are presented. Follow-up is ongoing but longitudinal FPG was available for interim analysis among the first n=100 recall-eligible participants (mean follow-up time=2±0.3 years). Mixed-effects regressions evaluated FPG time trends across baseline bacterial levels. All analyses were adjusted for cardiometabolic risk factors. Results: Prediabetes prevalence was 18% (54 of 300). RRs(95%CI) summarizing associations between bacteria and pre diabetes were as follows: Aa=2.48[1.34,4.58], p=0.004; Pg=3.41[1.78,6.58], p=0.0003; Td=1.99[0.992,4.00], p=0.052 and Tf=1.95[1.0,3.84], p=0.05; An=0.46[0.25,0.85], p=0.01. Among participants with high baseline values of Pg or Tf, FPG increased by ~2.5 mg/dl during follow-up (all p-values<0.05) while no FPG progression was observed among participants with low baseline bacterial levels. Conclusion: Periodontopathic microbiota are associated with both prevalent prediabetes and longitudinal plasma glucose increase among diabetes-free adults.

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Diet quality and periodontal disease: Results from the oral infections, glucose intolerance and insulin resistance study (ORIGINS)

Journal Of Clinical Periodontology ◽

10.1111/jcpe.13450 ◽

2021 ◽

Vol 48 (5) ◽

pp. 638-647

Author(s):

Francesco DeMayo ◽

Rebecca Molinsky ◽

Muna J. Tahir ◽

Sumith Roy ◽

Jeanine M. Genkinger ◽

...

Keyword(s):

Insulin Resistance ◽

Periodontal Disease ◽

Glucose Intolerance ◽

Diet Quality ◽

Oral Infections

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Subgingival Microbiota and Longitudinal Glucose Change: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS)

Journal of Dental Research ◽

10.1177/0022034519881978 ◽

2019 ◽

Vol 98 (13) ◽

pp. 1488-1496 ◽

Cited By ~ 2

Author(s):

R.T. Demmer ◽

P. Trinh ◽

M. Rosenbaum ◽

G. Li ◽

C. LeDuc ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Intolerance ◽

Statistical Significance ◽

Community Diversity ◽

P Value ◽

Rrna Gene ◽

Subgingival Plaque ◽

Oral Infections ◽

Glucose Levels ◽

Subgingival Microbiota

Microbial communities along mucosal surfaces throughout the digestive tract are hypothesized as risk factors for impaired glucose regulation and the development of clinical cardiometabolic disease. We investigated whether baseline measures of subgingival microbiota predicted fasting plasma glucose (FPG) longitudinally. The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 230 diabetes-free adults (77% female) aged 20 to 55 y (mean ± SD, 34 ± 10 y) from whom baseline subgingival plaque and longitudinal FPG were measured. DNA was extracted from subgingival plaque, and V3 to V4 regions of the 16S rRNA gene were sequenced. FPG was measured at baseline and again at 2 y; glucose change was defined as follow-up minus baseline. Multivariable linear models regressed 2-y glucose change onto baseline measures of community diversity and abundances of 369 individual taxa. A microbial dysbiosis index (MDI) summarizing top individual taxa associated with glucose change was calculated and used in regression models. Models were adjusted for age, sex, race/ethnicity, education, smoking status, body mass index, and baseline glucose levels. Statistical significance was based on the false discovery rate (FDR; <0.05) or a Bonferroni-corrected P value of 1 × 10-4, derived from the initial 369 hypothesis tests for specific taxa. Mean 2-y FPG change was 1.5 ± 8 mg/dL. Baseline levels of 9 taxa predicted FPG change (all FDR <0.05), among which Stomatobaculum sp oral taxon 097 and Atopobium spp predicted greater FPG change, while Leptotrichia sp oral taxon 498 predicted lesser FPG change (all 3 P values, Bonferroni significant). The MDI explained 6% of variation in longitudinal glucose change ( P < 0.001), and baseline glucose levels explained 10% of variation ( P < 0.0001). FPG change values ± SE in the third versus first tertile of the MDI were 4.5 ± 0.9 versus 1.6 ± 0.9 ( P < 1 × 10-4). Subgingival microbiota predict 2-y glucose change among diabetes-free men and women.

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The subgingival microbiome, systemic inflammation and insulin resistance: The Oral Infections, Glucose Intolerance and Insulin Resistance Study

Journal Of Clinical Periodontology ◽

10.1111/jcpe.12664 ◽

2017 ◽

Vol 44 (3) ◽

pp. 255-265 ◽

Cited By ~ 37

Author(s):

Ryan T. Demmer ◽

Alexander Breskin ◽

Michael Rosenbaum ◽

Aleksandra Zuk ◽

Charles LeDuc ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Intolerance ◽

Systemic Inflammation ◽

Oral Infections

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Plasma Trimethylamine-N-oxide and impaired glucose regulation: Results from The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS)

PLoS ONE ◽

10.1371/journal.pone.0227482 ◽

2020 ◽

Vol 15 (1) ◽

pp. e0227482 ◽

Cited By ~ 1

Author(s):

Sumith Roy ◽

Melana Yuzefpolskaya ◽

Renu Nandakumar ◽

Paolo C. Colombo ◽

Ryan T. Demmer

Keyword(s):

Insulin Resistance ◽

Glucose Intolerance ◽

Glucose Regulation ◽

Impaired Glucose Regulation ◽

Oral Infections

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SAT-616 Associations Of Body Mass Index And Waist Circumference In Young Adulthood With Later Life Incident Diabetes

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.045 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Nandini Nair ◽

Eric Vittinghoff ◽

Mark Pletcher ◽

Elizabeth Oelsner ◽

Norrina Allen ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Body Mass Index ◽

Young Adult ◽

Young Adulthood ◽

Cardiometabolic Risk ◽

Later Life ◽

Overweight And Obesity ◽

Incident Diabetes

Abstract Background: Overweight and obesity are known risk factors for incident diabetes, but it remains unclear if exposures during young adulthood (age 18 to 39 years) contribute to mid and late-life (age ≥40 years, collectively labeled here as “later-life”) risk of incident diabetes independent of later-life risk factor exposures. Objective: We sought to assess the independent associations between young adult exposures to overweight and obesity, as assessed by body mass index (BMI) and waist circumference (WC), with later-life incident diabetes, accounting for later-life exposures. Methods: We pooled data from six US cohorts (ARIC, CARDIA, CHS, Framingham Offspring, Health ABC, and MESA), and imputed life-course risk factor trajectories for BMI and WC, as well as for multiple cardiometabolic risk factors, annually from age 18 years to end of follow-up for each participant. Incident diabetes was defined by observed fasting blood glucose ≥126 mg/dL, non-fasting glucose ≥200, or use of diabetes medications. We used Cox proportional hazards models to examine the independent associations between time-weighted average exposures to BMI and WC during young adulthood and incident diabetes. We also performed mediation analyses to assess whether these associations were mediated by young adult exposures to other cardiometabolic risk factors (blood pressure, lipids, insulin resistance). Results: 30,780 participants were included (mean age at first in-person visit 53.1±16.2 years; 56.1% female). Over a 9-year median follow-up, 4,323 participants had incident diabetes. Both young adult BMI and WC were associated with diabetes risk in a dose-dependent manner, independent of later-life BMI and WC. Compared to BMI 18.5–24.9 kg/m2, hazard ratios (HR) for incident diabetes were 1.27 (95%CI: 1.14–1.41) and 1.99 (95%CI: 1.67–2.37) for BMI 25–29 kg/m2 and ≥30 kg/m2, respectively. Similarly, compared to normal WC (≤80 cm women; ≤94 cm men), the HRs were 1.42 (95%CI: 1.26–1.59) for WC 81-88cm (women)/95-102cm (men) and 2.13 (95%CI: 1.87–2.43) for WC >88cm (women)/>102cm (men). Young adult homeostatic model of insulin resistance (HOMA-IR) mediated 49% (95%CI: 23–76) and 44% (95%CI: 26–62) of the association between young adult BMI and WC with later-life incident diabetes, respectively. Conclusions: Elevated BMI or WC during young adulthood were independently associated with later-life incident diabetes, after accounting for later-life BMI and WC, with insulin resistance suggested as a key mediator.

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Iron metabolism is prospectively associated with insulin resistance and glucose intolerance over a 7-year follow-up period: the CODAM study

Acta Diabetologica ◽

10.1007/s00592-014-0646-3 ◽

2014 ◽

Vol 52 (2) ◽

pp. 337-348 ◽

Cited By ~ 25

Author(s):

Nick Wlazlo ◽

Marleen M. J. van Greevenbroek ◽

Isabel Ferreira ◽

Eugene H. J. M. Jansen ◽

Edith J. M. Feskens ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Intolerance ◽

Iron Metabolism

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Estimated glomerular filtration rate and cardiometabolic risk factors in a longitudinal cohort of children

Scientific Reports ◽

10.1038/s41598-021-91162-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sílvia Xargay-Torrent ◽

Elsa Puerto-Carranza ◽

Irene Marcelo ◽

Berta Mas-Parés ◽

Ariadna Gómez-Vilarrubla ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Blood Pressure ◽

Glomerular Filtration Rate ◽

Filtration Rate ◽

Cardiometabolic Risk ◽

Normal Weight ◽

Cardiometabolic Risk Factors ◽

Overweight Subjects

AbstractAssociations between glomerular filtration rate (GFR) and cardiometabolic risk factors have been reported in adult and pediatric patients with renal disease. We aimed to assess the relationship between the estimated GFR (eGFR) and cardiometabolic risk factors in apparently healthy children. A longitudinal study in 401 asymptomatic Caucasian children (mean age 8 years) followed up after 4 years (mean age 12 years). GFR was estimated using the pediatric form of the FAS-equation. Children were classified at baseline according to their obesity status (normal weight and overweight) and according to eGFR levels (lower, average, and higher). The association of eGFR with anthropometric data [body mass index (BMI) and waist], blood pressure [systolic (SBP) and diastolic (DBP)], metabolic parameters [glucose, insulin resistance (HOMA-IR) and serum lipids], and renal ultrasonography measurements were assessed at baseline and follow-up. Baseline eGFR associated with several cardiometabolic risk factors at follow-up including higher waist, SBP, HOMA-IR, and kidney size (all p < 0.0001) in both normal weight and overweight children. In multivariate analysis, baseline eGFR was independently associated with follow-up HOMA-IR and SBP in both normal weight and overweight subjects (model R2: 0.188–0.444), and with follow-up BMI and waist in overweight subjects (model R2: 0.367–0.477). Moreover, children with higher filtration rates at baseline showed higher waist, SBP, DBP, HOMA-IR and renal size both at baseline and follow-up. eGFR is related to insulin resistance, blood pressure and adiposity measures in school-age children. eGFR may help to profile the cardiometabolic risk of children.

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